APPLICANT S ABSTRACT: The objective of the proposed research is to identify genes involved in the etiology of alcohol dependence. The research will utilize a set of already collected families of alcoholics, including 250 sib pairs. These families were ascertained through male and female affected sib pairs and include at least one parent from each nuclear family. DNA and in-person diagnostic information are available for all of these individuals. The existence of this valuable resource will enable us to conduct a two-stage genome scan for the purpose of localizing alcoholism susceptibility genes, utilizing state-of-the-art automated genotyping. In the first stage, we will utilize markers spaced at approximately IO cM intervals to detect linkages greater than 1.5. These "hot spots" will be followed up with genotyping of multiple flanking markers at more densely spaced intervals (2 cM). In view of the significant resource which our sample represents, the proposed work has a potential for uncovering significant linkages between specific chromosomal regions and our alcoholism phenotype. The combined resources of our research team will situate us to initiate positional cloning of a gene, should significant positive linkages be found with our Stage I and Stage 11 genotyping endeavors.